Cushing's Disease page 2

Dr. Michael Richards

Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...

Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...

Hyperadrenocorticism, Cushing’s
disease, is caused by either a pituitary brain tumor or an adrenal gland tumor
in almost all cases. There may be a small percentage of dogs who have Cushing’s
disease due to overstimulation of the pituitary gland by the hypothalamus but
this is not a certainty at this time. Pituitary tumors are the most common cause
of Cushing’s disease, accounting for 80 to 85% of the cases of Cushing’s disease

When there is a pituitary tumor it
produces too much of the hormone that directs the adrenal glands to make
cortisones. When there is an adrenal gland tumor it produces cortisone
continuously without responding to the pituitary gland’s efforts to control the
cortisone levels in the body. The end result of either process is the same,
cortisol levels in the body rise beyond normal levels which leads to the
clinical symptoms. In many texts a standard acronym for dogs with pituitary
tumors causing Cushing’s disease is PDH, standing for pituitary dependent
hyperadrenocorticism. For dogs with adrenal tumors the acronym most commonly
used is ATH or adrenal tumor hyperadrenocorticism.

Cushing’s disease affects female
dogs more commonly than male dogs. Approximately 60% of the dogs with Cushing’s
disease are female. In addition, female dogs are also more likely to have an
adrenal gland tumor causing the Cushing’s disease. Of dogs who have adrenal
tumors about 65% are female.

Almost all dogs with Cushing’s
disease are over 6 years of age and approximately 75% of dogs diagnosed with
Cushing’s disease are over 9 years of age. It is important to remember this if a
young dog is diagnosed with the disease. There are documented cases in young
dogs, some under two years of age, but it is a rare finding. Almost all cats
with Cushing’s disease are over 9 years of age.

PDH is a disease primarily of
small dogs. About 75% of the cases of PDH occur in dogs weighing less than 20kg
(44 lbs). Large breed dogs are less likely to develop Cushing’s disease overall
but when they do develop it they have a higher incidence of adrenal gland tumors
than smaller dogs with perhaps 20% of the cases of Cushing’s disease in larger
dogs being adrenal in origin.

The symptoms of Cushing’s disease
may include any of the following problems: increased drinking and urinating,
increased appetite, panting, a pendulous appearance to the abdomen, increased
susceptibility to urinary bladder and skin infections, decreased exercise
tolerance, weight gain, hair loss (often in a symmetrical pattern), testicular
atrophy, increased pigmentation of the skin, thinning of the skin (especially
noticeable in cats), muscle weakness, calcium deposits in the skin (calcinosis
cutis) or less commonly in internal organs and a bulging appearance to the eyes.
Failure to regrow hair that has been shaved occurs with both
hyperadrenocorticism and hypothyroidism fairly commonly.

It is very important to recognize
that there are probably no dogs who have all the clinical signs when they are
affected by Cushing’s disease. Most dogs probably have two to three symptoms and
there are a number of dogs who have no clinical signs, or at least none that are
recognized by their owners. Hyperadrenocorticism does not generally cause an
obvious illness. Pets may seem normal except for the presence of a symptom such
as increased thirst.

In cats the clinical signs can be so
subtle that it is likely most cats with Cushing’s disease go undiagnosed and
that the disorder is found only when there is a good reason other than clinical
signs to look for it. The single most common reason that Cushing’s disease is
diagnosed in cats is difficulty regulating insulin requirements in cats with
diabetes. When it is very difficult to establish a maintenance dosage for
insulin for a cat with diabetes there is a chance that Cushing’s disease is
present, as well. This is how most cases of Cushing’s disease in cats have
been discovered.

The most prevalent sign of Cushing’s disease
in cats is probably thinning of the skin. This can be very noticeable in some
cats as the skin develops an almost translucent appearance and just feels thin
when touched. A small number of cats develop thinning of the skin to the point
where it tears easily and these injuries prompt the diagnostic process necessary
to identify the disease.

Unusual complications sometimes
occur with Cushing’s disease in dogs, as well. A small number of dogs develop
severe muscular weakness (myotonia) that usually affect the rear legs
predominantly. This can lead to a stiff gait or to collapse of the rear limbs in
some dogs. Facial paralysis seems to be due to Cushing’s disease in a small
number of dogs. Just like cats, a few dogs with diabetes will be very hard to
regulate on insulin unless concurrent Cushing’s disease is controlled.

Since Cushing’s disease is the
overproduction of cortisone it is possible to create all the symptoms of the
disease by giving doses of cortisones, such as prednisone. This occurs most
commonly when prednisone is given on a daily basis or for very long periods of
time on an every other day basis. When a pet is being given a cortisone
containing medication and develops symptoms of Cushing’s disease it is referred
to as iatrogenic Cushing’s disease. This is a very different problem than
naturally occurring Cushing’s disease. The only time when this presents a
serious diagnostic challenge is when the veterinarian has no idea that
prednisone or other glucocorticoids are being administered.

Routine laboratory tests are not
very helpful in diagnosing Cushing’s disease but they can give some hints that
the disease is present. The most common routinely tested laboratory abnormality
that veterinarians associate with Cushing’s disease is an increase in alkaline
phosphatase levels. This is a very nonspecific test for Cushing’s disease but
when there is a rise in the alkaline phosphatase levels it is necessary to at
least think about the possibility that Cushing’s disease may be present.

Dogs with Cushing’s disease may
have slightly elevated white blood cell counts. Usually this is due to rise in
neutrophils. Blood sugar levels tend to be in the high normal to slightly higher
than normal levels in dogs. This sign is less useful in cats because cats can
elevate their glucose levels in response to stress, including the stress of
veterinary visits and drawing blood. Sometimes blood urea nitrogen (BUN) and
creatinine levels are decreased in dogs with Cushing’s disease. In most cases
these values are normal, however.

The clinical syndromes caused by
hypothyroidism and hyperadrenocorticism are similar enough that many dogs are
tested for both diseases when either one is suspected. It is important to note
that dogs who do have Cushing’s disease may have low thyroid hormone
measurements due to the Cushing’s disease. This means that it is not uncommon
for the lab values to indicate that both Cushing’s disease and hypothyroidism
appear to be present when in fact the thyroid levels are low due to the
Cushing’s disease and not because the dog actually has hypothyroidism. It can be
very difficult to decide whether to treat a dog for hypothyroidism when it also
has Cushing’s disease.

Diagnosing Cushing’s disease
requires specialized testing. There are a number of options for testing dogs,
all of which have some advantages and some disadvantages. At the present time
the majority of endocrinologists seem to favor using the low dose dexamethasone
suppression test (LDDS) over the ACTH response test but there is still some
disagreement over this. The urine cortisol:creatinine ratio can be a useful
screening test for Cushing’s disease but is not accurate enough to depend on for
treatment decisions. To give you some idea of the relative accuracy of these
tests it is necessary to discuss two values, sensitivity and specificity.

Sensitivity is the measurement of
how likely a test is to be positive when a pet has a disease. A test that is
100% sensitive will always detect the disease. Another way to think of this is
to consider the sensitivity as a measurement of how likely a negative result on
a test is to be accurate. If a test is 100% sensitive then any negative result
would be 100% accurate.

Specificity is the measurement of
how accurately a positive test result identifies pets who actually have the
disease. A test that is 80% specific will be accurate in identifying truly
positive individuals 80% of the time. Or to look at it the other way, if the
test is positive there is a 20% chance that the pet being tested doesn’t
actually have the disease being tested for.

The specificity and sensitivity of
the various tests for Cushing’s disease play a major role in determining the
usefulness of each of the tests. The low dose dexamethasone suppression test is
about 95% sensitive but is only about 70% specific. An ACTH response test is
approximately 80% sensitive but the specificity of the test has been very
variable in reported studies, with a low of 35% and a high of 80%. Urine
cortisol:creatinine ratios are very sensitive for detecting the possibility of
Cushing’s disease, probably at least 90% sensitive. This test has very low
specificity, though. Only about 20 to 25% of dogs with abnormal
cortisol:creatinine levels actually have Cushing’s disease. Some vets feel that
this is still a useful screening test, on the theory that a negative result is
very likely to be correct. This test is inexpensive compared to the other tests
so even though further testing would need to be done to confirm a positive
result it can still be viewed as a reasonable first step in the diagnostic
process since a dog with a negative test result is unlikely to have Cushing’s
disease.

It is possible to identify
pituitary tumors with MRI or CT scans. This isn’t a very economical test and the
sensitivity of the testing can be low when tumors are small. It is sometimes
possible to identify adrenal tumors with ultrasound examination.

It is much harder to accurately
diagnose Cushing’s disease in cats. There are several reasons for this but the
one with the most impact on testing appears to be the ability of cats to produce
high cortisol levels in response to stress. This ability makes it hard to get
good results from tests that use cortisol levels to measure the response to ACTH
or dexamethasone. Even though none of the tests work as well in cats as they do
in dogs, there is general agreement that the urine cortisol:creatinine level and
the LDDS tests probably work best at determining if Cushing’s disease is
present. It is very important to note that the “low dose” dexamethasone test
recommended for cats uses the dose of dexamethasone that is used for the “high
dose” test in dogs. Failure to use this higher dose usually results in a
meaningless test result.

In both dogs and cats it is
important not only to show that Cushing’s disease is present but to take the
next step and to determine whether the disease is caused by a pituitary gland
tumor or by an adrenal gland tumor. This type of testing is in a transition
state at the current time in veterinary medicine, at least in dogs.

In the past the best test for
determining the underlying cause of Cushing’s disease was thought to be a test
referred to as a high dose dexamethasone suppression test (HDDS). Using high
doses of dexamethasone it is possible to fairly reliably suppress any effect of
the pituitary gland on adrenal gland production of cortisols. Since it is
possible to rule out PTH if suppression occurs, the only dogs who do not respond
to the higher dose should be those with adrenal gland tumors. While the test
doesn’t work quite that well in real life it was still the best test for
differentiating between pituitary and adrenal origin Cushing’s disease until the
advent of the newer imaging technologies.

It is usually possible to
determine if the adrenal glands are enlarged by ultrasound examination and to
visualize tumors if they are present in most dogs. If it has been demonstrated
that Cushing’s disease is present this information can be used to determine if
adrenal or pituitary origin Cushing’s disease is most likely. Ultrasonagraphy
isn’t a very good initial test for Cushing’s disease because the changes may not
be pronounced in the case of PDH and any tumor visualized may or may not be
causing Cushing’s disease.

Computerized tomography (CT) or
magnetic resonance imaging (MRI) can both be used to identify pituitary gland
tumors if they are large enough. Many dogs do not have detectable tumors at the
time of initial diagnosis but most dogs with PDH will eventually develop a tumor
large enough to visualize by CT scan or MRI. This information applies about
equally to dogs and cats, in general.

Some veterinarians opt not to try
to differentiate between PDH and ATH based on testing. Insteady, they opt to
treat for PDH first in all cases. If the response to treatment is not as good as
they expect, they then make and effort to confirm that adrenal origin
hyperadrenocorticism is present. This can be a reasonable choice as long as
everyone is informed of the decision and the success or failure of treatment is
monitored closely. It is not ideal but it meets the economic needs of some
clients in a realistic manner.

The use of discrimination tests to
differentiate between pituitary and adrenal origin Cushing’s disease in cats is
not as well established. There is a protocol for doing a high dose dexamethasone
suppression (HDDS) test using urine samples collected at home over the course of
two or three days that looks like it may turn out to be the best test for
discriminating between PDH and ATH in cats. Alternatively, MRI or CT scans may
show pituitary gland tumors but this is not a very sensitive test.

At this point we have a patient
who has clinical signs consistent with Cushing’s disease and who has laboratory
results consistent with Cushing’s disease. In most cases we also have a pretty
good idea whether the Cushing’s disease is caused by an adrenal gland tumor or
by a pituitary brain tumor. It now becomes necessary to make treatment decisions
based on the information that has been obtained.

The first question that has to be
asked is whether treatment is even necessary. There is no well documented
evidence that suggests that treatment for Cushing’s disease, with the exception
of successful removal of solitary tumors, has an effect on life span after
diagnosis. Therefore, medical treatment of Cushing’s disease can be viewed as
optional if the clinical signs are not debilitating or causing significant
interference with the pet’s life style and surgery is not an option. Most dogs
and cats who are diagnosed with Cushing’s disease are brought to the
veterinarian’s because their symptoms have become a problem but for those that
aren’t it is reasonable to ask if treatment is necessary.

Surgical treatment for Cushing’s
disease has always been an option for patients with adrenal gland tumors. There
are a number of veterinarians who are comfortable attempting exploratory
abdominal surgery and removing adrenal gland tumors. Until recently surgery was
not considered to be an option for pituitary dependent Cushing’s disease in dogs
and cats because the surgery was considered to be too risky or too expensive for
veterinary medicine. Dr Meij at the Utrecht University in the Netherlands
developed a technique for successfully removing pituitary gland tumors which is
referred to as hypophysectomy. This surgery has survival rates comparable to
medical treatment now and other institutions are starting to offer it as an
alternative to medical treatment. I believe that most endocrinologists would
agree that hypophysectomy is the preferred treatment for PDH when the pet owner
can afford to pursue surgery and locating a surgical facility is not too
difficult.

Despite the fact that removal of
tumors from the adrenal gland has been a more widely available option there is
some argument over whether it is the best approach to adrenal origin tumors,
especially those that are suspected to have spread to other organs. Surgery of
the adrenal gland carries significant risks and it is estimated that It is
considered reasonable to use mitotane to treat adrenal tumors but the success
rates are low in comparison to many surgical procedures, especially when
malignant tumors are present. Overall the surgical success rate, defining 16
months of survival post-surgically as success, is about 50%. The success rate of
medical therapy is almost identical when using the same criteria for success.

Treatment options for cats with
either PDH or ATH origin Cushing’s disease are not as diverse. Cats do not
respond very well to medical therapy for Cushing’s disease. Therefore,
hypophysectomy is the preferred therapy. If that is not possible to arrange the
other option to consider in a cat is surgical removal of both adrenal glands.
This is a radical approach since it instantly produces hypoadrenocorticism (not
enough production of cortisols) and this has to be managed very carefully to
keep the patient alive. The mortality rate associated with surgery is about 50%
within a few days to weeks of surgery but for cats who live through this
initial period the surgery appears to work well.

While it is unusual, there have
been some well documented cases of spontaneous remission from Cushing’s disease.
This makes sense as spontaneous remission seems to occur with a number of
cancers. It isn’t something you can count on, but if your pet seems to recover
from previously diagnosed Cushing’s disease it is really possible that recovery
is truly happening.

If surgery can not be considered
there are medical treatment options. There are a number of medications that
have been used to treat Cushing’s disease but the three most commonly used
medications at the present time are selegiline (Anipryl Rx), mitotate (o,p’-DDD,
Lysodren Rx) and trilostane (Vetoryl Rx, not approved at this time for use in
the United States). Each of these drugs appears to have some advantages and
disadvantages so it is generally necessary to tailor treatment to the specific
needs of individual pets. It is important to recognize that medical treatment of
Cushing’s disease controls the symptoms but does not address the underlying
problem of a pituitary or adrenal gland tumor, with a few exceptions noted in
the paragraphs that follow.

Selegiline is approved for the
treatment of Cushing’s disease in dogs but it only works well in approximately
20% of dogs. In another 20% of dogs it works well enough that pet owners are
satisfied with the choice of medication even though it doesn’t completely
control symptoms of hyperadrenocorticism. Selegiline is considered to be a safe
medication and it is easy to use because follow up laboratory testing is not
nearly as important when using selegiline as when using mitotane or trilostane.
For this reason a number of veterniarians will try selegiline first when
treating a patient with uncomplicated Cushing’s disease, even though the odds
are stronger that it won’t work. One reason this can be a good choice is the
group of dogs who appear to have PDH that is due to overstimulation by the
hypothalamus. Theoretically it is possible to actually cure this group using
selegiline and some researchers believe they have seen this effect. If this does
happen it happens for a very small and select group of patients but this still
seems to justify trying selegiline when there are no major reasons not to.

Mitotane is a chemotherapeutic
agent that specifically targets the adrenal glands. It works by destroying
adrenal gland tissue, preventing the overproduction of cortisones by the adrenal
glands. Since some adrenal gland function is necessary for survival, it is
necessary to try to balance the amount of destruction that occurs against the
need for cortisone in the body. In order to do this, it is necessary to run ACTH
response tests frequently during the initial dosing period and then periodically
while the dog is being given mitotane. It is hard to overemphasize the
importance of this monitoring. There is a strong temptation to try to minimize
testing due to the expense and inconvenience but patients treated with mitotane
can die if too much adrenal tissue is damaged during the initial treatment stage
or during maintenance therapy. It is absolutely critical for good lines of
communication to exist between the veterinarian and pet owner when mitotane is
being used. Do not leave your veterinarian’s office until you thoroughly
understand exactly how your vet wants you to monitor your dog.

These are some things to consider
when using mitotane:

When first stating mitotane the
earliest indication it is working is a decrease in appetite. Any noticeable
decrease in appetite, even just being slow to start eating, is sufficient change
to alert your vet. Most veterinarians want you to stop the medication and
schedule a recheck visit as soon as any decrease in appetite is noted.

Mitotane makes some dogs nauseous.
Vomiting can be a sign of overdosage or of continuing the induction dose for too
long, so you should discuss all instances of vomiting with your vet. If after
doing so it seems likely that the medication is causing the vomiting rather than
overdosage, splitting the daily dose up can help. Twice daily dosing with
smaller amounts is often enough but the dose can be further divided if
necessary. Giving the pills with food helps to alleviate this problem, as well.

Mitotane should not be started in
a patient who is already vomiting, has diarrhea or seems to have a poor
appetite.

If a patient who is on maintenance
dosages of mitotane requires a planned surgery or if any other event occurs that
causes significant sress it is best to put the dog on prednisone or other
glucocorticoid medications for the stressful period. A few pets require
cortisone supplementation every day while using mitotane but most do not.

Trilostane is approved for use in
England but not in the United States. It is available in the U.S. through
compounding pharmacies and can be imported legally as an experimental drug if
proper procedures are followed. It works by inhibiting the production of
cortisone in the adrenal gland by interfering with conversion of cortisone
precursors into cortisone. In humans this effect seems to be variable but it is
not known if there is a similar problem in dogs, yet. It is possible to evaluate
the effect of trilostane using lab work and this is recommended. Trilostane is
more expensive than mitotane but over time the lower laboratory follow-up
requirements may make this expense easier to bear.

There are a number of possible
complications of medical treatment of Cushing’s disease. The most significant of
these is causing hypoadrenocorticism without noticing it. Even during the
maintenance dosing it is critical to report changes in appetite, vomiting,
diarrhea or marked decreases in water consumption to your veterinarian. Medical
treatment often works for a while and then seems to stop working, necessitating
adjustments in medication dosage or frequency of use. Some dogs who start out
with just pituitary origin Cushing’s disease go on to develop adrenal tumors and
this can complicate therapy. Obviously it is also possible for dogs with PDH to
develop AT origin hyperadrenocorticism. If you keep in contact with your
veterinarian and report changes as they occur, it is usually possible to work
through complications and to continue to successfully treat pets with Cushing’s
disease.

A number of people have asked if
it is possible to combine medical therapies for Cushing’s disease in dogs but
using mitotane or trilostane and selegiline as well. As far as I can tell there
is no reason that selegiline can not be combined with these other medications.
In a few instance in which I know this has been done the clients felt that they
were receiving benefits from both drugs. It is possible that this is an effect
that is independent of any effect that selegiline has on Cushing’s disease
directly, though. Selegiline is also approved for use in “canine cognitive
dysfunction” which is a senility problem in older dogs. It is likely that some
dogs who seem to respond better to therapy with selegiline and another
medication for Cushing’s disease actually has both problems, especially since
both of these problems are common in older dogs.

In cats the major reason that
Cushing’s disease is diagnosed is its adverse effect on the regulation of blood
glucose in cats who have both diabetes and Cushing’s disease. It is unlikely
that there would be nearly as much information on Cushing’s disease in cats if
this link had not been uncovered. It is important to understand that this
information doesn’t mean that all cats who are difficult to regulate on insulin
have Cushing’s disease. It is more likely that there is a problem with insulin
timing, dosage, type or use than that Cushing’s disease is present. However, if
after careful review of injection procedures, insulin type, timing of insulin
doses, diet and other factors there continues to be a problem with insulin
regulation it makes sense to look for Cushing’s disease. Acromegaly, another
hormonal disease, can also interfere with insulin regulation and must also be
considered.

If medical or surgical treatment
controls clinical signs, why do dogs and cats with Cushing’s disease die from
the disease? The simplest answer to this question is that the population of dogs
with Cushing’s disease can be said to have cancer in nearly 100% of cases and
the cancer is not generally removed surgically. Eventually the cancer causes
problems. This may be the strongest reason to opt for surgical treatment,
especially for pituitary origin hyperadrenocorticism but the truth is that at
the current time it is quite difficult to arrange for hypophysectomy because it
is done by so few surgeons. In the future this is likely to change and surgery
may become the most common treatment option. This may not cure all cases of PDH
since there are some malignant tumors but it at least offers the hope of an
actual cure.

There are other factors beside the
underlying cancers that can lead to serious complications, as well. Some dogs
with Cushing’s disease develop abnormal blood clotting, which can lead to
pulmonary embolisms or problems in other areas of the body. High blood pressure
(hypertension) is common in dogs with hyperadrenocorticism. Cushing’s disease
complicates a number of other older age diseases, such as diabetes, skin
infections, kidney or bladder infections and congestive heart failure. When
these other conditions are present they tend to be much more difficult to manage
in a patient with Cushing’s disease. Seizures and other neurologic signs can
occur when pituitary tumors enlarge.

There are no specific dietary
recommendation for pets with Cushing’s disease but it is theorized that they may
do better on reduced fat diets since there is a strong tendency towards obesity
in patients affected by Cushing’s disease. Some vets also favor the use of
anti-oxidants such as fish oils in the diet, on the theory that controlling
inflammation may help to slow the development of the underlying cancer.

Hyperadrenocorticism is a serious
problem in older dogs and it is likely that over time we will continue to
recognize it more and more in older cats, as well. It is a disorder that
requires close communication between a veterinarian and pet owner during both
the diagnostic and treatment periods. The importance of this communication can
not be overstated so if your pet is diagnosed with Cushing’s disease make sure
there is a veterinarian in the practice you chose to treat the disease who you
are comfortable talking with and who you understand fully. Managing
hyperadrenocorticism successfully can make a dog or cat feel much better,
increasing the quality of their life. When it is caused by benign tumors that
can be successfully removed there is a chance for a cure. As more veterinary
facilities become experienced in hypophysectomy this should be come a more
realistic option for many pets. Your vet can help you find a surgical facility
capable of this surgery if you want to consider this option now rather than in
the future.

Dr Mike Richards, DVM
10/2005

Hyperadrenocorticism ( Cushing's Disease)

Guide to Abbreviations in this issue:

HAC Cushing's disease or hyperadrenocorticism

PDH pituitary dependent hyperadrenocorticism

AT adrenal tumor (adrenal
gland origin hyperadrenocorticism)

ACTH adrenocorticotropic hormone

CRH corticotropin releasing
hormone

LDDS low dose dexamethasone
suppression (test)

HDDS high dose dexamethasone
suppression (test)

SAP serum alkaline phosphatase

PU/PD polyuria/polydipsia
(increased drinking and urination)

Several subscribers have written in the past month and asked that we
provide an update on hyperadrenocorticism (Cushing's disease). This is
a disorder that is common in older dogs and occurs much more rarely in
cats. All of the clinical signs of Cushing's disease can be produced by
administering corticosteroids, such as prednisone, chronically. When
a dog or cat has the symptoms of hyperadrenocorticism (HAC) but the cause
is corticosteroid use, the syndrome produced is referred to as "Cushing's-like
syndrome" in some textbooks.

When the adrenal glands are functioning normally, their action is regulated
by a feedback mechanism involving the level of cortisone in the blood stream,
the hypothalamus (part of the brain), the pituitary gland (another part
of the brain) and a hormone it produces, ACTH (adrenocorticotropic
hormone). When cortisone levels in the body decrease, the hypothalamus
produces a hormone CRH (corticotropin releasing hormone) that stimulates
the pituitary gland to release ACTH, which stimulates the adrenal gland
to produce cortisone. When cortisol levels in the bloodstream are high,
the hypothalamus and the pituitary gland stop the release of ACTH and the
adrenal gland stops releasing cortisones into the bloodstream. This is
a complex process and a lot can go wrong with it.

Problems within the pituitary gland account for about 90% of the
cases
of hyperadrenocorticism. The most common pituitary gland problem is
cancer.
There are several types of tumors that affect the pituitary gland, all
of which can lead to an overproduction of ACTH and Cushing's disease.
In studies of dogs with Cushing's disease that have brain imaging scans
using computerized tomography (CT) or magnetic resonance imaging (MRI)
between 50% and 75% of the endent, since the regulatory mechanism seems
less sensitive in older patients, making over stimulation of the
pituitary
gland more common in geriatric patients.

Adrenal gland cancer causes the remaining 10% of cases of hyperadrenocorticism
in dogs. The best treatment for adrenal gland cancer is probably removal
of the affected gland(s). Lab testing can help to determine whether HAC
is due to adrenal cancer or due to pituitary gland effects. It is best
to try to confirm if adrenal gland cancer is present using standard X-rays
or in some cases, ultrasound, CT or MRI scanning.

Hyperadrenocorticism is much less frequent in cats than in dogs. This
may be due to the fact that cats appear to be more resistant to the effects
of cortisone than dogs and therefore less likely to respond to the age
related stimulation of the hypothalamus and pituitary gland that seems
to contribute to the development of Cushing's disease in dogs.

Who develops Hyperadrenocorticism

The typical patient with Cushing's disease is over nine years of age
but it has been reported in dogs as young as six months of age. To give
some perspective on this, over 90% of the cases of HAC occur in patients
nine and over. In dogs there does not appear to be sex related predisposition
to this disorder. In cats the current information, from a small number
of patients, indicates that female cats are slightly more likely to have
Cushing's disease than males. The breeds most likely to develop HAC include
poodles, dachshunds, beagles, boxers, Boston terriers and German shepherds.

Cushing's-like syndrome occurs in patients who are given corticosteroids
such as prednisone in a manner that causes symptoms of hyperadrenocorticism.
Patients with itchy skin disease whose owners give them prednisone on a
daily basis rather than an every other day basis sometimes develop symptoms
of HAC. Dogs on chemotherapeutic dosages of prednisone may also develop
Cushing's-like syndrome. A less frequent cause of Cushing's symptoms in
dogs is the use of corticosteroid eye drops on a daily basis. The dose
seems too small to lead to problems but there are several reported cases
of Cushing's like syndrome from the use of cortisone ophthalmic drops.
Treatment consists of lowering the dosage or discontinuing the cortisone,
if possible.

What are the Signs of HAC

The most common symptom of Cushing's disease in dogs is increased drinking
(polydipsia) and increased urination (polyuria). You may see this in a
patient's record abbreviated as "PU/PD". Some clients notice the increased
drinking but see no corresponding increase in urination while other clients
notice that urination frequency and amount have changed but don't notice
a change in drinking behavior. Despite this, these conditions occur concurrently.
Variations in observing these clinical signs probably occur due to the
ability of some patients to stand more urine retention in the
bladder, the presence of incontinence that makes urination obvious
or the availability of water sources that are hard to monitor.

Many dogs have increased appetites due to the higher levels of cortisol
in the blood stream.

Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...